Pallidotomy-the ablation of neurons in the internal segment of the globus pallidus-is now the surgical procedure of choice for the treatment of medically refractory Parkinson's disease.2-14 However effective, the procedure may be complicated by hemianopsia, or even hemiparesis, due to inadvertent lesions to the optic tract and internal capsule adjacent to the pallidum. 5,15. Excitotoxins are well known to lesion neurons selectively while sparing glial cells and axonal fibers of passage. Chemopallidotomy-the ablation of neurons in the globus pallidus using an excitotoxin infused to brain-may potentially target neurons immediately adjacent the internal capsule and optic tract. However, intrathecal and systemic administration of excitotoxins in experimental animals has resulted in seizures, and lesions outside the expected volume of distribution of the toxin in brain. Here we propose to characterize the potential of a pharmacologic antagonist to an excitotoxin, administered intravenously, to (1) reverse excitotoxic chemopallidotomy in unilaterally parkinsonian macaques; (2) eliminate lesions outside the target volume of distribution; and (3) function as an anti-epileptogen. During these experiments, the capability of diffusion-weighted magnetic resonance imaging of interstitial brain infusion, as well as anatomic alternations in thalamic and brain nuclei due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, will be explored.